The primary goal of the research program project is to clarify the role of the arterial wall in the pathogenesis of atherosclerosis. The major objectives of the project are to elucidate (1) the role of hypertension and lipoproteins in the pathogenesis of atherosclerosis; (2) the role of the smooth muscle cell and endothelial cell in vascular permeability and the biosynthesis of connective tissue proteins, especially with regard to the pathogenesis of atherosclerosis and their relationship to lipid, lipoprotein and calcium deposition in the plaque: (4) the role of platelets and the platelet "release action" in atherosclerosis; (5) mechanisms involved in the accumulation of lipids and lipoproteins in the arterial wall. These mechanisms include influx, synthesis, degradation and transport of lipoproteins in the arteries. (6) Role of physico-chemical changes of lipid and lipoproteins in atherosclerosis; (7) role of lipid and lipoprotein interactions with acid mucopolysaccharides, connective tissue proteins and calcium in atherosclerosis. The proposed programs will be carried out in subhuman primates (cynomolgus monkey) with experimental atherosclerosis and/or hypertension and in smooth muscle cells and endothelial cells grown in cell culture. These studies which include correlations of biochemical and ultrastructural function also are directed toward clarifying the role of nutritional factors and other etiological factors in the pathogenesis of atherosclerosis.